Effect of ketogenic diet for drug-resistant epilepsy on immunological cells.

BACKGROUND AND AIM OF THE WORK: Ketogenic diet (KD) is one of the treatments in drug-resistant epilepsy (DRE). The current study aimed at assessing the effect of KD-induced ketosis on different immunological cells since ketosis is reported to affect neutrophil function. METHODOLOGY: We recruited 21 pediatric patients diagnosed with DRE assigned to start KD. Anthropometric measurements, complete blood picture with differential count, phagocytic function, lymphocyte subsets, and IgG estimation were estimated initially and after 6 months of KD. RESULTS: There were no differences between the initial total leucocytic, neutrophil, and lymphocytic counts as well as the lymphocyte subsets, and the values after 6 months of KD. IgG values showed significant increase yet the values were still within the reference ranges. For the innate immune system, the phagocytic index was assessed and it showed a marked statistical reduction in patients after KD. CONCLUSION: KD has no effect on neutrophil and lymphocytic counts as well as the number of adaptive and immune cells; nevertheless, it causes a reduction in phagocytic index in DRE. Accordingly, further detailed study for the full immunological profile and function is needed to ensure the safety of this therapeutic line and correlate it with the clinical history.

Polymorphisms of the receptor for advanced glycation end products as vasculopathy predictor in sickle cell disease.

BACKGROUND: The genetic variants of the receptor for advanced glycation end products (RAGE) gene have been associated with vascular disease risk. The objective of this work was to explore the association of three single-nucleotide polymorphisms (SNPs) of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD. METHODS: The study was conducted on 40 children with SCD and 40 healthy children served as controls. All participants were genotyped for the three studied RAGE polymorphisms by polymerase chain reaction (PCR). RESULTS: Regarding 374T/A polymorphism, the frequency of TA, TT genotypes and T allele were higher in patients (p < 0.001). T allele was associated with higher incidence of sickling crisis and stroke (p < 0.05). In the subgroup analyses of 429T/C polymorphism, an association between C allele and SCD vascular complications was observed (p < 0.05). Concerning the frequency of G82S genotypes of RAGE, GG variant was detected in 39 (97.5%) of the patients, as compared with 40 (100%) of controls (p = 0.3). A regression analysis proved that HbS%, serum ferritin, and the -374T and 429C alleles were significant independent predictors of frequent sickling episodes (p < 0.05). CONCLUSIONS: The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD. IMPACT: The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD patients. To our knowledge, our study is the first exploring the association of three single-nucleotide polymorphisms of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD. Early identification of patients carrying these genetic variants might be of great importance not only to identify subjects at risk of vasculopathy but also to direct them to RAGE-targeted treatments.

Impact of Additional Chromosomal Aberrations Present at Diagnosis on Outcome of Adolescent and Young Adult Chronic Myeloid Leukemia Patients: A Single Center Experience.

Studying the influence of additional chromosomal aberrations (ACAs) present at diagnosis on the outcome of adolescent and young adult (AYA) chronic myeloid leukemia (CML) patients as it has not been addressed previously. Eighty-six AYA CML patients have been analyzed for occurrence of ACAs at diagnosis through performing bone marrow karyotyping. All patients received imatinib mesylate upon diagnosis of CML. Overall response, molecular response, survival status, progression and occurrence of events were monitored during the follow up period. There was a statistically significant difference between patients with and without ACAs regarding overall response (P = 0.049). There was insignificant difference between the two groups regarding achievement of major molecular response (MMR) (P = 0.594), MR4 (P = 0.282) and MR4.5 (P = 0.704). There was a significant difference between patients with and without ACAs regarding time to MMR (P = 0.042) and time to MR4 (P = 0.048) but not regarding time to MR4.5 (P = 0.065). There was insignificant impact of ACAs at diagnosis on overall survival (P = 0.152), progression free survival (P = 0.112), failure free survival (P = 0.114), event free survival (P = 0.194) and alternative treatment free survival (P = 0.731). The presence of ACAs at diagnosis does not signal worse prognosis in AYA CML patients but it may delay molecular response to imatinib mesylate.

MiR-615-5p depresses natural killer cells cytotoxicity through repressing IGF-1R in hepatocellular carcinoma patients.

miR-615-5p was characterized by our group as a tumour suppressor. IGF-1 R activates a downstream signalling pathway, well characterized in liver cells, however, its role in immunity especially Natural Killer cells (NKs) remains vague. This study aimed at investigating the regulatory role of miR-615-5p on IGF signalling and its impact on NKs cytotoxicity in HCC. Our results showed an upregulation in miR-615-5p and IGF-1 R in NKs of 130 HCC patients compared to 35 controls. Forcing the expression of miR-615-5p, repressed IGF-IR, attenuated NKs cytotoxicity, decreased CD56dim, increased CD56bright NK subsets and reduced the cytotoxic markers NKG2D, TNF-α and perforins. It repressed NKG2D ligand (ULBP2) in Huh-7 cells. In conclusion, miR-615-5p represses IGF-1 R in NKs and their target hepatocytes; however, it has a contradicting impact on HCC progression on both cell types. These findings might pave the way for better understanding the role of microRNAs in NKs function and HCC immune-pathogenesis.

Contradicting interplay between insulin-like growth factor-1 and miR-486-5p in primary NK cells and hepatoma cell lines with a contemporary inhibitory impact on HCC tumor progression.

In this study, an impaired natural killer (NK) cell cytolytic activity in 135 hepatocellular carcinoma (HCC) patients parallel to a reduced expression level of insulin-like growth factor (IGF)-1 in NK cells of HCC patients has been revealed. Ectopic expression of miR-486-5p, a direct upstream regulator of IGF-1, restored the endogenous level of IGF-1 in NK cells of HCC patients, thus augmenting its cytolytic activity against Huh7 cells in an opposite manner to the IGF-1 siRNAs. Unorthodoxly, over-expression of miR-486-5p in target hepatocytes resulted in the repression of IGF-1, suppression of Huh7 cells proliferation and viability in a similar pattern to the IGF-1 siRNAs. Therefore, this study highlights a potential role of IGF-1 in modulating cytolytic potential of NK cells of HCC patients. miR-486-5p acts in a cell-specific manner, differentially modulating IGF-1 expression in NK cells and their target hepatocytes with a contemporary inhibitory impact on HCC progression.